Campanumoea javanica Bl. activates the PI3K/AKT/mTOR signaling pathway and reduces sarcopenia in a T2DM rat model  

中药土党参激活PI3K/AKT/mTOR信号通路并减少2型糖尿病大鼠骨骼肌减少症

作　　者：Xiangyu Zuo Rongfei Yao Linyi Zhao Yinjiang Zhang Binan Lu Zongran Pang 左祥宇;姚荣飞;赵麟毅;张印江;鲁碧楠;庞宗然(中央民族大学)

机构地区：[1]School of Pharmacy,Minzu University of China,Beijing 100081,China

出　　处：《Acupuncture and Herbal Medicine》2022年第2期99-108,共10页针灸和草药（英文）

基　　金：supported by the National Natural Science Foundation of China(Grant No.:82074394)。

摘　　要：Objective: Sarcopenia causes loss of skeletal muscle and function, thus seriously affecting the physical function and quality of life in the elderly. This article discusses the specific molecular mechanism and ameliorating effects of Tudangshen(TDS) on sarcopenia in elderly rats with type 2 diabetes mellitus(T2DM).Methods: Elderly Sprague-Dawley(SD) rats were randomly selected and fed with a high-fat diet combined with an intraperitoneal injection of streptozotocin to establish T2DM model. The model rats were stratified and randomly divided into the model group,metformin group, TDS high-dose group, TDS medium-dose group, and TDS low-dose group according to blood glucose combined with body weight, and the same batch of old SD rats was set as the normal control group. The effects of TDS in an elderly T2DM sarcopenia rat model were evaluated by observing the body positions of the rats, analyzing blood biochemistry, testing exercise capacity, and pathologically staining sectioned gastrocnemius muscle tissues. The molecular mechanisms of the effects were analyzed using quantitative real-time polymerase chain reaction and western blotting.Results: TDS has no statistically significant effect on blood glucose, insulin and glycosylated serum protein in aged rats with T2DM, but it can reduce levels of glycosylated serum protein, total cholesterol, triglycerides, and low-density lipoprotein;it improves pathological changes in rat gastrocnemius muscle tissues, and increases muscle cell activity in elderly rats with T2DM and sarcopenia. TDS also promoted the upregulation of the expression of mammalian target of rapamycin(mTOR)/protein kinase B(PKB/AKT)/phosphatidylinositol 3-kinase(PI3K)/ribosomal protein S6 kinase/eukaryotic initiation factor 4 E binding rotein1 mRNA in rats and triggered an increase in corresponding protein levels.Conclusions: TDS alleviated muscle decline in elderly rats with T2DM by activating the PI3 K/AKT/mTOR signaling pathway and regulating the synthesis of corresponding proteins.目的探讨土党参对老年2型糖尿病大鼠骨骼肌肌量减少的改善及其分子机制作用。方法随机选取老年SD大鼠,采用高脂饲料喂养联合腹腔注射链脲佐菌素建立老年2型糖尿病模型。将成模大鼠按血糖结合体重分层随机分为模型组、二甲双胍组、土党参高剂量组、土党参中剂量组和土党参低剂量组,另设同批次老年SD大鼠作为正常对照组。各组分别给予对应药物治疗,给药干预4周后检测各组大鼠体重、腓肠肌重量、血生化指标,观察腓肠肌切片病理改变,考察土党参对老年2型糖尿病大鼠骨骼肌减少的改善作用;采用实时荧光定量PCR法检测mTOR/Akt/PI3K/s6k1/4ebp1的mRNA表达,采用蛋白质印迹法(WB)检测mTOR/Akt/PI3K/s6k1/4ebp1的蛋白表达,分析土党参产生作用的分子机制。结果土党参对老年2型糖尿病大鼠血糖、胰岛素和糖化血清蛋白水平的改善不如二甲双胍明显,但可以可降低总胆固醇、甘油三酯和低密度脂蛋白的水平,提高高密度脂蛋白的水平;并且改善小鼠腓肠肌组织细胞形态,增加老年2型糖尿病大鼠骨骼肌细胞活性。土党参上调大鼠腓肠肌mTOR/Akt/PI3K/s6k1/4ebp1 mRNA的表达,促进相应蛋白表达水平的升高。结论土党参可能是通过激活PI3K/AKT/mTOR信号通路,调节相应蛋白的合成,缓解老年2型糖尿病大鼠骨骼肌肌量减少的症状。

关 键 词：Campanumoea javanica Bl. SARCOPENIA Tudangshen Type 2 diabetes mellitus PI3K/AKT/MTOR 

分 类 号：R285.5[医药卫生—中药学]